title: RhoA and RhoC differentially modulate estrogen receptor α recruitment, transcriptional activities, and expression in breast cancer cells (MCF-7).
abstract: OBJECTIVE
  RhoA and RhoC are closely related, small GTPases that are clearly involved in breast cancer tumorigenesis. Nonetheless, their specific roles in the control of estrogen receptor alpha (ERα) activities have not been elucidated.
  
  
  METHODS
  We used siRNA sequences to specifically down-regulate RhoA and RhoC expression in ERα-positive breast adenocarcinoma MCF-7 cells. We then analyzed the consequences of down-regulation on ERα expression, ERα recruitment to the promoters of four target genes, and the mRNA levels of those genes.
  
  
  RESULTS
  We demonstrated that RhoA and RhoC clearly and similarly modulated ERα recruitment to the vitellogenin estrogen responsive element (ERE) present in a luciferase reporter gene and to the promoters of progesterone receptor (PR), cathepsin D, and pS2 genes. Besides, RhoA up-regulated the ERE-luciferase reporter gene activity and PR mRNA expression and tended to down-regulate cathepsin D and pS2 mRNA expression. Conversely, RhoC inhibition had no significant effect at the mRNA level. Furthermore, RhoA inhibition, and to a lesser extent RhoC inhibition, increased ERα expression. No alteration in ERα mRNA levels was observed, suggesting potential post-translational control.
  
  
  CONCLUSIONS
  Taken together, our results strongly suggest that RhoA and RhoC play different, but clear, roles in ERα signaling. These GTPases are definitely involved, along with RhoB, in ERα recruitment and, to some extent, ERα cofactor balance. We hypothesize a differential role of RhoA in breast cancer tumors that depend on hormone status.
authors.affiliation: INSERM U563 and UMR1037, Institut Claudius Regaud, 20-24 rue du pont St Pierre, 31052, Toulouse Cedex, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Malissein
authors.forename: Elise
authors.initials: E
authors.lastname: Meunier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lajoie-Mazenc
authors.forename: Claire
authors.initials: C
authors.lastname: Médale-Giamarchi
authors.forename: Florence
authors.initials: F
authors.lastname: Dalenc
authors.forename: Sophie F
authors.initials: SF
authors.lastname: Doisneau-Sixou
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020218:Response Elements; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: D047628:Estrogen Receptor alpha; D034741:RNA, Small Interfering; C066737:RHOA protein, human; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein